ArticleLiver international : official journal of the International Association for the Study of the Liver2023
Increased let-7d-5p in non-alcoholic fatty liver promotes insulin resistance and is a potential blood biomarker for diagnosis.
Article in Liver international : official journal of the International Association for the Study of the Liver, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.
- The use of circulating miRNAs for the diagnosis, prognosis, and personalized treatment of MASLD.Journal of physiology and biochemistry · 2025Pooled it
- MicroRNAs modulated by DPP-4 inhibitor and bedtime NPH insulin therapy in individuals with type 2 diabetes.Frontiers in endocrinology · 2025Trial
- Consolidating Clinical Insights and Uncovering Novel Regulatory Mechanisms of Exosomal MicroRNAs in Obesity and Metabolic Dysfunction Associated Steatotic Liver Disease: A Systematic Review and Bioinformatics Analysis.Food science & nutrition · 2026Review
- Extracellular Vesicles: Orchestrators of Intrahepatic and Systemic Crosstalk in Metabolic Dysfunction-Associated Steatotic Liver Disease.Pharmaceutics · 2026Review
- From Bench to Bedside: Multifunctional Nanoplatforms in the Fight Against Non-alcoholic Fatty Liver Disease.International journal of nanomedicine · 2026Review
- Exploring the Therapeutic Mechanism of Xiehuo Pingtu San in Treating Thyroid Eye Disease Based on Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation.International journal of endocrinology · 2026Article
- Extracellular Vesicles miRNome Profiling Reveals miRNAs Engagement in Dysfunctional Lipid Metabolism, Chronic Inflammation and Liver Damage in Subjects With Metabolic Dysfunction-Associated Steatotic Liver Disease.Alimentary pharmacology & therapeutics · 2025Article
- Serum microRNA Profiles and Pathways in Hepatitis B-Associated Hepatocellular Carcinoma: A South African Study.International journal of molecular sciences · 2024Review
- Modulation of MicroRNAs and Exosomal MicroRNAs after Dietary Interventions for Obesity and Insulin Resistance: A Narrative Review.Metabolites · 2023Review
- MicroRNAs and Nonalcoholic Steatohepatitis: A Review.International journal of molecular sciences · 2023Review
- The Role of miRNAs and Epigenetic Factors in Non-Alcoholic Fatty Liver Disease - a Systematic Review.Current health sciences journalReview
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
BACKGROUND AND
aimsThe molecular mechanisms driving non-alcoholic fatty liver disease (NAFLD) are poorly understood; however, microRNAs might play a key role in these processes. We hypothesize that let-7d-5p could contribute to the pathophysiology of NAFLD and serve as a potential diagnostic biomarker.
methodsWe evaluated let-7d-5p levels and its targets in liver biopsies from a cross-sectional study including patients with NAFLD and healthy donors, and from a mouse model of NAFLD. Moreover, the induction of let-7d-5p expression by fatty acids was evaluated in vitro. Further, we overexpressed let-7d-5p in vitro to corroborate the results observed in vivo. Circulating let-7d-5p and its potential as a NAFLD biomarker was determined in isolated extracellular vesicles from human plasma by RT-qPCR.
resultsOur results demonstrate that hepatic let-7d-5p was significantly up-regulated in patients with steatosis, and this increase correlated with obesity and a decreased expression of AKT serine/threonine kinase (AKT), insulin-like growth factor 1 (IGF1), IGF-I receptor (IGF1R) and insulin receptor (INSR). These alterations were corroborated in a NAFLD mouse model. In vitro, fatty acids increased let-7d-5p expression, and its overexpression decreased AKT, IGF-IR and IR protein expression. Furthermore, let-7d-5p hindered AKT phosphorylation in vitro after insulin stimulation. Finally, circulating let-7d-5p significantly decreased in steatosis patients and receiver operating characteristic (ROC) analyses confirmed its utility as a diagnostic biomarker.
conclusionsOur results highlight the emerging role of let-7d-5p as a potential therapeutic target for NAFLD since its overexpression impairs hepatic insulin signalling, and also, as a novel non-invasive biomarker for NAFLD diagnosis.
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